Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan

Our plain-English summary of Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan, by Y. Kurokawa, S. Takayama, Y. Konishi, et al (Environmental Health Perspectives, 1986).

The study

• Authors: Y. Kurokawa, S. Takayama, Y. Konishi, Y. Hiasa, S. Asahina, M. Takahashi, A. Maekawa, Y. Hayashi
• Journal: Environmental Health Perspectives
• Published: 1986;69:221-35
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Long-term in vivo carcinogenicity tests of potassium bromate (KBrO3), sodium hypochlorite (NaClO), and sodium chlorite (NaClO2) have been conducted in Japan from 1977 to 1985. In these investigations, groups of approximately 50 male and 50 female F344 rats or B6C3F1 mice were given solutions of the compounds as their drinking water ad libitum at two dose levels determined on the basis of preliminary 13-week tests. Control animals were given distilled water. The carcinogenic potential of KBrO3 was tested by administering doses of 500 or 250 ppm to rats for 110 weeks. Significantly elevated incidences of renal cell tumors in males and females and mesotheliomas of the peritoneum in males as compared to controls were observed. When female mice were given KBrO3 at doses of 1000 or 500 ppm for 78 weeks, no significant differences in tumor incidences between experimental and control groups were apparent. NaClO was administered to male and female rats, respectively, at doses of 1000 or 500 ppm and 2000 or 1000 ppm for 104 weeks. In mice, NaClO was given at doses of 1000 or 500 ppm to either sex for 103 weeks. The incidences of tumors in NaClO-treated and control animals of both sexes were not significantly different in both rat and mouse studies. NaClO2 was given to rats of both sexes at a dose of 600 or 300 ppm for 85 weeks. No statistically significant differences were observed in the incidences of tumor formation between NaClO2-treated and control groups of both sexes. NaClO2 was administered to mice at a concentration of 500 or 250 ppm for 85 weeks. In males, the combined incidences of hyperplastic nodules and hepatocellular carcinomas of the liver in a low-dose group, and adenomas and adenocarcinomas of the lung in a high-dose group, were marginally increased compared to controls (p less than 0.05). However, these incidences in treated males were within the range of values of historical control data in our program. We concluded that KBrO3 was carcinogenic in rats of both sexes. NaClO was not carcinogenic in either rats and or mice under the conditions of the present studies. Although NaClO2 was shown to be noncarcinogenic in rats, the results for mice were evaluated as inconclusive. Also the results of two-stage mouse skin carcinogenesis using KBrO3, NaClO, and NaClO2 are presented. The necessity for further testing of oxidant chemicals to determine potential carcinogenic and/or promoting effects is suggested in view of the recently proposed role of active oxygen species in carcinogenesis.

In plain English

This article reported long-term cancer tests in Japan, 1977 to 1985, of potassium bromate, sodium hypochlorite and sodium chlorite. It does not study asbestos. About 50 rats or mice per sex per group drank water with a chemical at one of two doses; controls drank distilled water. In rats given potassium bromate at 500 or 250 ppm, kidney tumors affected 88% and 60% of males and 80% and 56% of females, versus 6% and 0% of controls. Peritoneal mesotheliomas occurred in 28 of 46 high-dose, 17 of 52 low-dose and 6 of 53 control males. Female mice given potassium bromate, and animals given sodium hypochlorite, showed no significant tumor increases. Neither did sodium chlorite in rats, a test stopped at week 85 by infection. In male mice it showed marginal increases in combined hyperplastic liver nodules and carcinomas at the low dose and lung adenomas and adenocarcinomas at the high dose, though the authors noted these fell within historical control ranges. The authors concluded that potassium bromate was carcinogenic in rats of both sexes and judged the sodium chlorite mouse results inconclusive.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiments: long-term carcinogenicity tests in which the chemicals were given in drinking water at two dose levels, with distilled-water control groups
• Who was studied: F344 rats and B6C3F1 mice of both sexes (about 50 per sex per group), aged 4 to 6 weeks at the start, tested in Japan from 1977 to 1985. The potassium bromate mouse test used only female mice. The sodium hypochlorite mouse controls were 73 males and 72 females.
• Exposure: Potassium bromate (KBrO3): 500 or 250 ppm in drinking water for rats (the male high dose was reduced to 400 ppm at week 60), and 1000 or 500 ppm for female mice. Sodium hypochlorite (NaClO): 1000 or 500 ppm for male rats, 2000 or 1000 ppm for female rats, and 1000 or 500 ppm for mice. Sodium chlorite (NaClO2): 600 or 300 ppm for rats and 500 or 250 ppm for mice. No asbestos exposure was studied.
• Main results:
  • Rats given potassium bromate for 110 weeks: renal cell (kidney) tumors developed in 46 (88%), 32 (60%) and 3 (6%) of males, and in 39 (80%), 28 (56%) and 0 (0%) of females, at 500, 250 and 0 ppm. The treated groups differed significantly from controls (p less than 0.001).
  • Male rats given potassium bromate: mesotheliomas of the peritoneum were found in 28 of 46 (printed as 59%) at 500 ppm, 17 of 52 (33%) at 250 ppm and 6 of 53 (11%) controls. These counts are among males surviving longer than 72 weeks. Both treated groups differed significantly from controls (p less than 0.001 and p less than 0.05).
  • Female mice given potassium bromate at 1000 or 500 ppm for 78 weeks: no significant differences in tumor-bearing animals compared with controls.
  • Sodium hypochlorite: no significant compound-related increases in tumor incidence in any organ of treated rats of either sex. No statistically significant differences in treated mice.
  • Sodium chlorite in rats (study ended at week 85): no statistically significant differences in tumor-bearing animals between treated and control groups of either sex.
  • Sodium chlorite in male mice: combined liver hyperplastic nodules and hepatocellular carcinomas were significantly higher in the low-dose group, 22 (47%) versus 7 (20%) in controls (p less than 0.05). Lung adenomas and adenocarcinomas were significantly higher in the high-dose group (p less than 0.05). The authors noted these rates were within the range of their program's historical control data.
• The authors' conclusion: The authors concluded that potassium bromate was carcinogenic in rats of both sexes and that sodium hypochlorite was not carcinogenic in rats or mice under the conditions of these studies. They found sodium chlorite noncarcinogenic in rats and judged its mouse results inconclusive.
• Limitations the authors state:
  • The potassium bromate mouse test used only females, and the sodium chlorite rat test was stopped at week 85 because of infection.
  • In the sodium chlorite mouse test, control males died earlier than treated males because of severe fighting and were not included in the effective numbers.
  • The significant increases in sodium chlorite-treated male mice were seen only in benign tumors and fell within the range of historical control data.

Topics

Medical terms in this study, explained in our Lexicon: Chlorite, Carcinogenic, Mesothelioma, Peritoneum, Carcinoma, Adenocarcinoma, Carcinogenesis.

Related studies

• Identification of chlorite and serpentine in cosmetic or pharmaceutical talc — A.M. Blount, A.H. Vassiliou (1983)
• Interpretation of the carcinogenicity of amosite asbestos and ferroactinolite on the basis of retained fiber dose and characteristics in vivo — P.M. Cook, L.D. Palekar, et al. (1982)
• Tests for carcinogenicity of asbestos — W.E. Smith, L. Miller, et al. (1965)
• Long-term toxicity of naturally occurring asbestos in male Fischer 344 rats — J.M. Cyphert, M.A. McGee, et al. (2016)
• Correlations between chemically related site-specific carcinogenic effects in long-term studies in rats and mice — J.K. Haseman, A.M. Lockhart (1993)
• In vivo studies on genotoxicity and cogenotoxicity of ingested UICC anthophyllite asbestos — C. Varga, G. Horváth, et al. (1996)

Browse more research in Environmental Health Perspectives, or return to medical research.